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Biomedical subjects

M M Khan

Publications and source records attributed to M M Khan.

At least 19 recordsLinked to original sources
PubMed2007

The impact of political context upon the health policy process in Pakistan.

BACKGROUND: Analysis of the political context is important for the understanding of a health policy and its success, because contextual factors may significantly influence the health policy process and health. This article describes how the political context in Pakistan influences the health policy process. METHODS: We used qualitative research methods based on document analysis and interviews of relevant actors in analysing the impact of the political context on the health policy process. Document analysis included policy documents and official reports of the health ministries, health-related departments and international agencies. Interviewees included relevant actors involved in the health policy process at local, provincial, national and international levels. RESULTS: Pakistan has experienced unbalanced power structures and frequent changes in government, which has disturbed health resources and has resulted in a centralized health system that hinders wider participation and disrupts health policy-making, planning and implementation. CONCLUSION: It is concluded that the political context has had a negative influence on the health policy process in Pakistan.

Government↗
PubMed2006

Loss of Sef (similar expression to FGF) expression is associated with high grade and metastatic prostate cancer.

Fibroblast growth factors (FGF), and in particular FGF8, have been strongly implicated in prostate carcinogenesis. This study investigated the expression of Sef, a key inhibitory regulator of FGF signalling, in prostate cancer. In a panel of cell lines, hSef was detected in both androgen-dependent and independent cells but was significantly reduced in highly metastatic derivative clones. hSef expression was not influenced by androgenic stimulation. Forced downregulation of hSef by siRNA increased FGF8b induced cell migration (P=0.02) and invasion (P=0.007). Reduced hSef levels also enhanced FGF8b stimulated expression of MMP9 (P=0.005). mRNA in situ hybridization revealed hSef expression in 80% (8/10) of benign biopsies but in only 69% (23/33) of Gleason sum 4-7 and 35% (10/28) of Gleason sum 8-10 cancer biopsies (P=0.004). Quantitative PCR of microdissected glands confirmed this trend (P=0.001). hSef was expressed in 69% (27/39) of non-metastatic tumours but in only 18% (2/11) of metastatic tumours (P=0.004, n=50). hSef expression was next correlated with earlier data on FGF8b expression in a subgroup of cancers. In this cohort, 86% (19/22) of high-grade cancers expressed FGF8 but only 31% (7/22) expressed hSef. Positive FGF8 expression but a loss of hSef was observed in 88% (7/8) of metastatic tumours. In contrast, metastasis was evident in only 10% (1/10) of tumours, which co-expressed both FGF8 and hSef (P<0.001). These results suggest evidence that hSef is downregulated in advanced prostate cancer and might facilitate an enhanced tumorigenic response to FGFs. Further research into the role of hSef in cancer cell signalling and the mechanism of its downregulation may contribute to more effective targeting of growth factors in prostate cancer.

Androgens↗
PubMed2005

Evidence that prostate gonadotropin-releasing hormone receptors mediate an anti-tumourigenic response to analogue therapy in hormone refractory prostate cancer.

Gonadotropin-releasing hormone analogue (GnRHa) therapy is an established method of androgen withdrawal in the treatment of prostate cancer. The present study investigated if the expression of prostate GnRH receptors (GnRHRs) might influence the response to GnRHa. GnRHR protein expression was first studied in a panel of prostate cancer cell lines. In androgen-dependent cells, GnRHR expression was unchanged following acute or chronic androgen withdrawal. In these cells, GnRHa significantly inhibited androgen-induced cell proliferation (p = 0.01). In contrast, GnRHa was unable to further suppress basal levels of cell proliferation induced by androgen withdrawal. In androgen-independent prostate cancer cells, variable levels of GnRHR expression were observed. In these cells, GnRHa treatment blocked cell proliferation (p = 0.001) and invasion (up to 70%) induced by fibroblast growth factor stimulation. Crucially, this effect was only evident in cells that expressed high levels of the GnRHR. GnRHa treatment also significantly inhibited the ability of these cells to recover from a cytotoxic insult (50% inhibition). The clinical significance of prostate GnRHR was tested by immunohistochemistry in a preliminary cohort of patients treated with GnRHa or surgical castration. There was no association between GnRHR expression and pathological grade, clinical stage, time to PSA nadir (p = 0.82) (n = 35) or progression to hormone refractory disease (p = 0.22) (n = 21), irrespective of the treatment method. GnRHa therapy in the presence of high GnRHR expression however, was found to be associated with longer disease-specific survival (mean survival 85 months, p = 0.002). In contrast, high GnRHR expression was not associated with survival among surgically castrated patients (mean survival 50 months, p = 0.7). Taken together, these data support the notion of a functional interaction between GnRHa and the GnRHR, which results in an anti-tumourigenic effect on prostate cancer cells. Findings from this report have direct implications for the use of GnRHR as a novel therapeutic target in hormone refractory prostate cancer.

Antineoplastic Agents, Hormonal↗
PubMed2005

Sequential versus concurrent paclitaxel and carboplatin for the treatment of advanced non-small cell lung cancer in elderly patients and patients with poor performance status: results of two Phase II, multicenter trials.

The primary objective of these trials was to determine the 1-year survival of advanced non-small cell lung cancer (ANSCLC) patients (> or =70 years with PS 0-2 or > or =18 years with PS 2) receiving sequential paclitaxel and carboplatin (P --> C) or concurrent P + C. The secondary objectives were assessment of toxicities and quality of life. A total of 121 patients with NSCLC were treated. P--> C patients received paclitaxel (80 mg/m(2)) weekly x 3, followed by 1 week of rest; these 4-week cycles were repeated until relapse. At relapse, patients received carboplatin (AUC = 5, IV) on Day 1 of each 3-week cycle until evidence of further progression or lack of improvement. P + C patients received paclitaxel (80 mg/m(2)) and carboplatin (AUC = 2), weekly x 3, followed by 1 week of rest, until relapse. Patients in both studies were premedicated prior to paclitaxel administration. Sequential P + C resulted in a median survival of 8.2 months (range: <1-18.8) and P + C patients had a median survival of 9.2 months (range: <1-22.0). In both groups (P--> C) and P + C), the 1-year survival was 31%. For patients treated sequentially, treatment-related AEs (TRAE, > or =Grade 3) included fatigue (7%), neuropathy (5%), and leukopenia and diarrhea (3%, each). Grade 4 AEs were limited to neutropenia, febrile neutropenia, and sepsis (1 episode each). For patients receiving concurrent P + C, TRAE included neutropenia and leukopenia (15%, each) and shortness of breath and bilateral bone pain (10%, each). Leukopenia (n = 2) and neutropenia (n = 1) were the only Grade 4 events reported. The analysis of quality of life (QOL) questionnaires indicated that there were no obvious differences between treatment groups during the study. These drugs and treatment schema were well-tolerated when administered in the community setting and resulted in survival rates that were similar to what is reported in the literature with combination therapy administered to "high risk" patients. Finding the optimal chemotherapy regimen, that can be tolerated, remains a challenge in elderly patients.

Age Factors↗
PubMed2005

Polio immunization policy in Mexico: economic assessment of current practice and future alternatives.

The World Health Organization recommends that all children aged less than 5 years should be vaccinated against polio through intensive immunization programmes as well as routine immunization. A national immunization week (NIW) was held in February 2002 in the Monterrey district of Mexico. A prospective micro-costing study was conducted to measure the total cost to the state of the NIW, the cost profile, and the ratio of cost per immunization contact to cost per dose of oral polio vaccine (OPV), and to compare OPV and inactive polio vaccine (IPV) in economic terms. Two scenarios were used as the basis for calculation. The cost of volunteers was excluded from the "lower-cost scenario" and included in the "upper-cost scenario". The total cost of the NIW was USD 100,454 for the lower-cost scenario and USD 156,614 for the upper-cost scenario. The major part of the costs was personnel costs (67.30 and 77.53% of the total costs in the lower- and upper-cost scenario, respectively). The ratio of cost per immunization contact to cost per dose of OPV was 6.45 for the lower-cost scenario and 10.05 for the upper-cost scenario. Changing from the current OPV-based intensive and routine schedule to a sequential IPV-OPV routine schedule would save USD 14.52 per vaccinated child, and changing to a full IPV routine schedule would save USD 9.41 per vaccinated child.

Cost-Benefit Analysis↗
PubMed2005

Effect of aerobic exercise on patients with primary fibromyalgia syndrome.

Sixty eight adult patients of fibromyalgia were included in this prospective study from the Outpatient Department of Physical Medicine and Rehabilitation of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka during the period of January 2003 to June 2003. Study samples were assigned into two treatment groups: Group A (n = 38) with exercise by static bicycle and aerobic walking in addition to tricyclic antidepressant and analgesic and Group B (n = 30) was non exercise group, treated with tricyclic antidepressant and analgesic only. The total duration of treatment was 16 weeks. Pre-treatment (week 0) and post treatment (week 16) evaluation was performed in both groups. Evaluation parameters included pain grade, number of trigger points, occurrence of arousal at night, frequency of micturition and global evaluation by the physician. After 16 weeks, mean improvement of exercise group and non exercise group was 48% and 39% respectively but this difference was not statistically significant. Therefore, from this study it was observed that aerobic exercise showed no significant benefit to fibromyalgia patients.

Exercise↗
PubMed2004

Unnecessary cesarean delivery in Louisiana: an analysis of birth certificate data.

OBJECTIVE: The purpose of this study was to explore the temporal trends and factors that are associated with cesarean deliveries and potentially unnecessary cesarean deliveries. STUDY DESIGN: The Louisiana birth certificate database was evaluated to identify a total of 57 potential indications/risk factors and maternal demographic factors that are associated with methods of delivery over the period from January 1993 to December 2000. A cesarean delivery without any potential indications/risk factors in the birth certificate was classified as unnecessary. RESULTS: The primary cesarean delivery rate decreased and the repeat cesarean delivery rate increased significantly during the study period. But neither the absence nor the presence of potential indications/risk factors accounted for these changes. The average potentially unnecessary primary and repeat cesarean deliveries in Louisiana were 17 and 43, respectively, per 100 cesarean deliveries over the years 1993 through 2000. CONCLUSION: The proportions of potentially unnecessary cesarean deliveries are relatively high in Louisiana. It is important to explore the influence of nonclinical factors on unnecessary cesarean delivery to reduce the cesarean rates.

Birth Certificates↗
PubMed2003

Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment.

A role of indices of oxidative stress, oxidative injury, and abnormal membrane phospholipid, specifically the phospholipid essential polyunsaturated fatty acids (EPUFAs) metabolism has been suggested based on studies in separate groups of patients with or without medication. The current study investigated the relationship between these biochemical measures in first-episode psychotic patients (N=16) at baseline and after 6 months of antipsychotic treatment (N=5 each with risperidone and olanzapine) and compared them to matched normal subjects. The indices of oxidative stress included: antioxidant enzymes; superoxide dismutase, glutathione peroxidase and catalase; and the oxidative injury as the levels of plasma lipid peroxides. The key membrane EPUFA's been; linolenic acid, arachidonic acid, nervonic acid, docosapentaenoic acid and docosahexaenoic acid. Furthermore, the changes in these biochemical measures were correlated with clinical symptomatology. Data indicated that, at baseline, reduced levels of antioxidant enzymes were associated with increased plasma lipid peroxides and reduced membrane EPUFAs, particularly omega-3 fatty acids. Furthermore, these biochemical measures normalized after 6 months of antipsychotic treatment. Parallel-improved psychopathology indicated that membrane EPUFA status might be partly affected by oxidative damage, which together may contribute to the pathophysiology and thereby, psychopathology of schizophrenia. These data also support the augmentation of antipsychotic treatment by supplementation with a combination of antioxidants and omega-3 fatty acids.

Adult↗
PubMed2003

Anaesthesia for Caesarean section: a survey in a UK region from 1992 to 2002.

Data are presented for anaesthesia for Caesarean section (CS) in the South-west Thames region of the UK. The CS rate rose from 12.7% in 1987 to 24.2% in 2002. The rate of increase shows no sign of slowing. The rate of regional anaesthesia (RA) for elective CS rose from 69.4% in 1992 to 94.9% in 2002, when spinal anaesthesia was used for 86.6% of cases. This may limit the opportunities to teach other anaesthetic techniques. The rate of RA for emergency CS rose from 49.3% in 1992 to 86.7% in 2002. There is an unacceptable rate of failure of RA for both elective and emergency CS, 1.3% of RAs for elective CS and 4.9% of RAs for emergency CS were converted to general anaesthesia.

Anesthesia, Epidural↗
PubMed2003

Antipsychotic drugs differentially modulate apolipoprotein D in rat brain.

Apolipoprotein-D (apoD), a member of the lipocalin family of proteins, binds to arachidonic acid and cholesterol among other hydrophobic molecules. Recently, elevated apoD levels have been reported in the post-mortem brains, as well as plasma, of schizophrenic patients and in rodent brains after chronic treatment with clozapine (CLOZ). These findings and the evidence for altered membrane lipid metabolism in schizophrenia suggest that apoD may have a role in the pathophysiology of illness, and also in the differential clinical outcome following treatment with typical and atypical antipsychotic drugs. Here, we compared the effects of these antipsychotics on the expression of apoD in rat brain. Chronic treatment with typical antipsychotic, haloperidol (HAL) reduced apoD expression in hippocampus, piriform cortex and caudate-putamen (p = 0.027-0.002), whereas atypical antipsychotics, risperidone (RISP) and olanzapine (OLZ) increased (p = 0.051 to < 0.001 and p = 0.048 to < 0.001, respectively) apoD expression. In hippocampus, HAL-induced changes were present in CA1, CA3 and dentate gyrus, however, apoD levels in motor cortex were unchanged. There were also very dramatic effects of HAL on the neuronal morphology, particularly, cellular shrinkage and disorganization with the loss of neuropil. Post-treatment, either with RISP or OLZ, was very effective in restoring the HAL-induced reduction of apoD, as well as cellular morphology. Similarly, pre-treatments were also effective, but slightly less than post-treatment, in preventing HAL-induced reduction of apoD. The increased expression of apoD by atypical antipsychotics may reflect a novel molecular mechanism underlying their favorable effects compared with HAL on cognition, negative symptoms and extra-pyramidal symptoms in schizophrenia.

Animals↗
PubMed2003

Depressive disorder: diagnosis and management in general practice in Pakistan.

OBJECTIVE: To formulate guidelines for diagnosis and management of depressive illness in general practice in Pakistan. METHODS: Using guidelines developed through research in primary care, this article explains how depressive illness could be diagnosed using diagnostic and statistical manual (DSM) criteria and managed systematically at general practice level in Pakistan. RESULTS: Diagnosing depression accurately and choosing the right anti-depressant and giving it for adequate length of time are crucial factors in effective management of depression. CONCLUSION: Depressive illness can be diagnosed and managed effectively in general practice in Pakistan and only a minority of patients would need to be referred to psychiatrists.

Antidepressive Agents↗
PubMed2002

A comparative study of effects of cigarette and bidi smoking on respiratory function tests.

The effects of cigarette and bidi smoking on pulmonary function tests have been studied in 90 healthy males from North India Forced vital capacity (FVC), peak expiratory flow rate (PEFR), forced expiratory volume in 1 sec (FEV) were determined in 30 nonsmokers (as control group), 30 cigarette smokers and 30 bidi smokers. All the above pulmonary function parameters were found to be lower among smokers as compared to nonsmokers. Moreover, the decrease in the pulmonary function tests was greater in cigarette smokers as compared to bidi smokers.

Adult↗
PubMed2001

Modulation in the photosensitivity of albumin-bound bilirubin.

Exposure of BR-albumin complexes to visible light at pH 8.0 led to a change in the fluorescence intensity at 525 nm, which was found to be different for different serum albumins. Whereas a complex of BR with human serum albumin (HSA) showed a marked increase in fluorescence upon photoirradiation, BR-sheep serum albumin (SSA) complex failed to produce a marked increase. On the other hand, a complex of pig serum albumin (PSA) with BR produced a remarkable decrease in fluorescence upon photoirradiation. Equilibration of these complexes with approximately 20 mM chloroform for 1 h resulted in alteration in the photoinduced fluorescence. These photoinduced fluorescence modulations were found to be concentration dependent. Photoirradiation of BR-HSA complex led to a significant decrease in the positive CDCEs of the bisignate CD spectra in a time dependent manner that can be reconciled, to a significant extent, in the presence of chloroform. Taken together, all these results suggest that chiroptical properties/stability of albumin-bound BR varies with albumin species, protein concentration and the presence of chloroform.

Albumins↗
PubMed2001

PML-RARalpha alleviates the transcriptional repression mediated by tumor suppressor Rb.

A fusion between the promyelocytic leukemia (PML) protein and the retinoic acid receptor-alpha (RARalpha) results in the transforming protein of acute promyelocytic leukemia, PML-RARalpha. PML has growth-suppressive properties and is localized within distinct nuclear structures referred to as nuclear bodies. PML participates in numerous cellular functions, including transcriptional activation, apoptosis, and transcriptional repression, whereas PML-RARalpha blocks these functions. However, the role played by PML-RARalpha in leukemogenesis remains unclear. Here we report that PML is required for transcriptional repression mediated by the tumor suppressor Rb. Rb interacts with the histone decaetylase (HDAC) complex containing co-repressors and represses the transcription of the E2F target genes. Overexpression of PML enhanced Rb-mediated repression. The degree of Rb-mediated repression was weakened by injecting anti-PML antibodies and was lower in Pml-deficient mouse embryonic fibroblasts. PML-RARalpha inhibited Rb-mediated repression, and two co-repressor-interacting sites on the PML-RARalpha molecule were required for this activity. Furthermore, PML-RARalpha blocked the interaction between Rb and HDAC. Thus, aberrant binding of PML-RARalpha to co-repressor-HDAC complexes may inhibit their association with Rb, resulting in the abrogation of Rb activity. Thus, the disruption of Rb-mediated repression may be a contributory factor in leukemogenesis.

Animals↗
PubMed2001

The Ski protein family is required for MeCP2-mediated transcriptional repression.

DNA methylation is essential for development in the mouse and plays an important role in inactivation of the X chromosome and genomic imprinting. MeCP2 is the founder member of a family of methyl-CpG-binding proteins. MeCP2 directly binds to the co-repressor mSin3, which interacts with class I histone deacetylase, recruiting them to methyl-CpG regions to suppress transcription. Here, we report that MeCP2 directly binds to two co-repressors, c-Ski and N-CoR, in addition to mSin3A, and that the c-Ski, which is encoded by the c-ski proto-onocogene, is required for MeCP2-mediated transcriptional repression. The two regions of c-Ski, including the C-terminal coiled-coil region, interact with the transcriptional repression domain in the center of the MeCP2 molecule. The immunostaining signals for c-Ski and MeCP2 overlap in the nuclear heterochromatin region, suggesting the co-localization of the two proteins. The degree of transcriptional repression mediated by a Gal4-MeCP2 fusion protein was abrogated by overexpression of the putative dominant negative form of c-Ski. Furthermore, injection of antibodies against c-Ski and Sno almost completely abolished the transcriptional repression mediated by the Gal4-MeCP2 fusion protein. These results suggest that the ski gene family is involved in methyl CpG-mediated transcriptional repression.

Blotting, Western↗
PubMed2001

Understanding the role of internal lysine residues of serum albumins in conformational stability and bilirubin binding.

The role of internal lysine residues of different serum albumins, viz. from human, rabbit, goat, sheep and buffalo (HSA, RbSA, GSA, SSA and BuSA), in conformational stability and bilirubin binding was investigated after blocking them using acetylation, succinylation and guanidination reactions. No significant change in the secondary structure was noticed whereas the tertiary structure of these proteins was slightly altered upon acetylation or succinylation as revealed by circular dichroism (CD), fluorescence and gel filtration results. Guanidination did not affect the native protein conformation to a measurable extent. Scatchard analysis, CD and absorption spectroscopic results showed marked reductions (5-21-fold decrease in K(a) and approximately 50% decrease in the CD Cotton effect intensity) in the affinity of albumins for bilirubin upon acetylation or succinylation whereas guanidination produced a small change. Interestingly, monosignate CD spectra of bilirubin complexed with GSA, SSA and BuSA were transformed to bisignate CD spectra upon acetylation or succinylation of internal lysine residues whereas spectra remained bisignate in the case of bilirubin bound to acetylated or succinylated derivatives of HSA and RbSA. When probed by CD spectroscopy, bilirubin bound to acetylated or succinylated derivatives of GSA and SSA rapidly switched over to native albumins and not vice versa. These results suggested that salt linkage(s) contributed by internal lysine residue(s) play an important role in the high-affinity binding of bilirubin to albumin and provide stability to the native three-dimensional conformation of the bound pigment. Chloroform severely decreased the intensity of both positive and negative CD Cotton effects of bilirubin complexed with acetylated or succinylated derivatives of all albumins which otherwise increased significantly in the case of bilirubin complexed with native and guanidinated albumin derivatives, except the bilirubin-RbSA complex which showed a small decrease in intensity. These results suggest that the presence of salt linkage(s) in bilirubin-albumin complexation is(are) crucial to bring about effective and efficient stereochemical changes in the bound pigment by co-binding of chloroform which seems to have at least one conserved binding site on these albumins that is shared with bilirubin.

Acetylation↗
PubMed2001

Regulation of interleukin-10 secretion by histamine in TH2 cells and splenocytes.

Interleukin-10 is a potent suppressive factor that down-regulates cellular immune response via inhibition of the production of TH1 cytokines. Histamine shifts the TH1/TH2 balance from TH1 to TH2 cytokines making the effects of histamine on IL-10 secretion an important factor in this switch. This study was designed to assess the role of histamine in the regulation of IL-10 production and the involvement of PKA and STAT factors in this process. TH2 cells (D10.G4.1) and AKR/j splenocytes were pretreated with histamine at a concentration range of 10(-8)-10(-5) M for 1 h and then activated with PMA + ionomycin or anti-CD3 for 24 h. The supernatants were collected and tested for IL-10 content by ELISA. Histamine stimulated IL-10 production in TH2 cells in a dose-dependent manner that was reversed by both H1- and H2-receptor antagonists and by PKA inhibitors H8 and Rp-cAMPS. Tyrphostin also reversed the stimulation of IL-10 secretion by histamine, indicating that STAT factors were involved in this process. The up-regulation of IL-10 production by histamine in splenocytes was accompanied by inhibitory effects of histamine on IFN gamma production. The pretreatment of splenocytes with histamine in the presence of anti-IL-10 abrogated histamine-mediated inhibition of IFN gamma production suggesting that the effects of histamine on IFN gamma secretion were regulated by IL-10 in multi-cell system.

Animals↗